Project description:We examined the antifungal activity of artemisinin against Aspergillus fumigatus (A. fumigatus), a pathogenic filamentous fungus responsible for allergic and invasive aspergillosis in humans and analyzed transcript profiles of the fungus on exposure to Artemisinin. A. fumigatus spores were cultured for 48 h and then treated with artemisinin (at MIC50 concentration) or solvent control (DMSO) for 3 h to study its transcriptomic profiles.
Project description:Genomic DNA from five strains, Aspergillus fumigatus Af71, Aspergillus fumigatus Af294, Aspergillus clavatus, Neosartorya fenneliae, and Neosartorya fischeri, were co-hybridized with that of Aspergillus fumigatus Af293 and compared.
Project description:Candida albicans is the most prevalent human pathogenic fungus, responsible for drug-resistant and fatal invasive infections which show an increasing trend in the past two decades. A promising new therapeutic approach involves NFAP2, an antifungal protein secreted by Neosartorya (Aspergillus) fischeri. NFAP2 exhibits potent antifungal activity on both planktonic and biofilm-forming Candida cells in vitro and in vivo. Despite this promising feature,the exact antifungal mechanism of NFAP2 remains in the shadow which hampers its therapeutic application. Based on our recent observations, we suppose that NFAP2 is taken up by Candida cells, and has a long-term growth-slowing effect. Our objective was to understand the molecular mechanism of the long-term growth slowing effect of NFAP2 in C. albicans, therefore the transcriptome of the NFAP2-treated (below the minimum inhibitory concentration) C. albicans SC5314 cultures was compared to that of the untreated ones.The transcriptional responses to NFAP2 were further characterized using functional enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways.
Project description:Aspergillus fumigatus is the most important pulmonary fungal pathogen and is able to cause several diseases collectively called aspergillosis. Conidia is the most important infection structure making the initial contact with the human host. Here, we used a phylogenomic approach comparing proteins present in the A. fumigatus conidial surface, two closely related non-pathogenic species A. fischeri and A. oerlinghausenensis, and the far-related pathogenic A. lentulus. We were able to identify 62 proteins specifically expressed on A. fumigatus conidial surface. We deleted 42 of the encoding-genes and observed that many of them have altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. We demonstrated that one of these genes encoding a glycosylasparaginase is modulating IL-1β levels and is important for the infection in an immunocompetent murine model. Our results provide opportunities for characterizing A. fumigatus effectors important for evasion and modulation of the immune response.
Project description:Acyl-homoserine lactone (acyl-HSL) quorum sensing was first discovered in Vibrio fischeri where it serves as a key control element of the seven-gene luminescence (lux) operon. Since this initial discovery, other bacteria have been shown to control hundreds of genes by acyl-HSL quorum sensing. Until recently, it has been difficult to examine the global nature of quorum sensing in V. fischeri. However, the complete genome sequence of V. fischeri is now available and this has enabled us to use transcriptomics to identify quorum-sensing regulated genes and to study the quorum-controlled regulon of this bacterium. In this study, we used DNA microarray technology to identify over two-dozen V. fischeri genes regulated by the quorum sensing signal N-3-oxohexanoyl-L-homoserine lactone (3OC6-HSL). Keywords: Comparison of transcriptome profiles
Project description:Aspergillosis covers a range of infections cause by Aspergillus species, and in many cases can be life threatening. Individuals with weakened immune systems are particularly at risk. Dendritic cells were derived from patients with allergic brochopulmonary aspergillosis (ABPA), chronic cavitary pulmonary aspergillosis (CCPA), and asthma, as well as from healthy donors. Each sample was split in two, and one sample from each pair was cultured with Aspergillus fumigatus. RNA-sequencing was used to assess transcriptional changes in the human cells in response to pathogen challenge. Many genes known to be important in immunity were found to exhibit differential expression after fungal challenge between healthy and diseased individuals, including chemokines and C-type lectins.
Project description:COVID-19-associated pulmonary aspergillosis (CAPA) is a frequent, severe superinfection with the fungus Aspergillus affecting critically ill COVID-19 patients. The pathophysiology of this infection is still largely unknown. We performed an explorative study by performing single-cell RNA sequencing (scRNA-seq) on 43 bronchoalveolar lavage (BAL) fluid samples from 39 mechanically ventilated COVID-19 patients.
